Pcbp2, also known as Poly (rC)-binding protein 2, is an RNA-binding protein and a cytosolic Fe(II) chaperone. It plays crucial roles in various biological processes such as mRNA metabolism, iron transport, and regulation of multiple signaling pathways, which are vital for normal cell function and are associated with numerous diseases [1,2,6].

In pancreatic β cells, Pcbp2-deficient mice showed defects in insulin secretion, calcium flux, insulin granule ultrastructure, and exocytosis, highlighting its role in maintaining β cell function and adaptation to glucose [1]. In malignant mesothelioma, knockdown of Pcbp2 decreased TfR1 and FTH expression, inhibited cell proliferation, and increased sensitivity to ferroptosis, indicating its role in ferroptosis-resistance during carcinogenesis [2]. In glioma, Pcbp2 promoted tumor progression and metastasis, reduced oxidative-stress-induced apoptosis by suppressing the cGAS/STING pathway, and its knockdown inhibited glioma cell proliferation, migration, and invasion while promoting apoptosis [3,5]. In breast cancer, depletion of Pcbp2 protein inhibited cell proliferation, colony formation, migration, invasion, and in vivo tumor growth and metastasis [4]. In prostate cancer, in vitro experiments showed that Pcbp2 promoted cell proliferation, migration, and invasion by inhibiting the cGAS-STING pathway [7].

In conclusion, Pcbp2 is essential for maintaining normal physiological functions in multiple cell types. Its dysregulation is involved in diseases like type 2 diabetes, malignant mesothelioma, glioma, breast cancer, and prostate cancer. Gene-knockout or knockdown models in these studies have been instrumental in uncovering Pcbp2's role in disease-related biological processes, providing potential therapeutic targets for these diseases.

References:

1. Haemmerle, Matthew W, Scota, Andrea V, Khosravifar, Mina, Ghanem, Louis R, Stoffers, Doris A. 2024. RNA-binding protein PCBP2 regulates pancreatic β cell function and adaptation to glucose. In The Journal of clinical investigation, 134, . doi:10.1172/JCI172436. https://pubmed.ncbi.nlm.nih.gov/38950317/

2. Yue, Lin, Luo, Yaguang, Jiang, Li, Sekido, Yoshitaka, Toyokuni, Shinya. 2022. PCBP2 knockdown promotes ferroptosis in malignant mesothelioma. In Pathology international, 72, 242-251. doi:10.1111/pin.13209. https://pubmed.ncbi.nlm.nih.gov/35089637/

3. Chen, Xiang, Yu, Mingchuan, Xu, Wei, Liu, Yu, Luo, Jun. 2022. PCBP2 Reduced Oxidative Stress-Induced Apoptosis in Glioma through cGAS/STING Pathway by METTL3-Mediated m6A Modification. In Oxidative medicine and cellular longevity, 2022, 9049571. doi:10.1155/2022/9049571. https://pubmed.ncbi.nlm.nih.gov/36267817/

4. Wang, Xiaonan, Guo, Qianying, Wang, Hao, Tan, Sheng, Wu, Zhengsheng. 2020. PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E. In Molecular cancer research : MCR, 19, 86-98. doi:10.1158/1541-7786.MCR-20-0390. https://pubmed.ncbi.nlm.nih.gov/33037085/

5. Mao, Jianhui, Sun, Zhaosheng, Cui, Yongjian, Hao, Zhenmin, Zheng, Lei. 2019. PCBP2 promotes the development of glioma by regulating FHL3/TGF-β/Smad signaling pathway. In Journal of cellular physiology, 235, 3280-3291. doi:10.1002/jcp.29104. https://pubmed.ncbi.nlm.nih.gov/31693182/

6. Yanatori, Izumi, Kishi, Fumio. 2018. DMT1 and iron transport. In Free radical biology & medicine, 133, 55-63. doi:10.1016/j.freeradbiomed.2018.07.020. https://pubmed.ncbi.nlm.nih.gov/30055235/

7. Zhou, Zeng, Li, Tiewen, Zhang, Yichen, Zhang, Yu, Ruan, Yuan. 2025. PCBP2 promotes immune evasion via cGAS-STING pathway in biochemical recurrence of prostate cancer. In APL bioengineering, 9, 016112. doi:10.1063/5.0250173. https://pubmed.ncbi.nlm.nih.gov/40051782/